1. Field of the Invention
This invention relates to a process for reversing or preventing secondary aldosteronism and potassium depletion induced by diuretic therapy and to compositions useful for this purpose.
2. Description of the Prior Art
Most clinically useful oral diuretic agents not only cause loss of water from an animal organism, but also excretion of electrolytes (natriuresis, kaluresis, etc.). The loss of sodium is frequently desirable in the treatment of edematous conditions associated with heart failure and hypertension, but loss of potassium is undesirable as it causes muscular weakness and paralysis, and respiratory and cardiac disturbances. Examples of such diuretics are furosemide, ethacrynic acid and diuretics of the benzothiadiazine type, e.g. chlorothiazide, hydrochlorothiazide, flumethiazide, hydroflumethiazide, bendroflumethiazide, benzthiazide, cyclothiazide, methyclothiazide, polythiazide, trichlormethiazide; and related substances, e.g. chlorthalidone and quinethazone. Diuretics which are carbonic anhydrase inhibitors, e.g. acetazolamide, dichlorphenamide, ethoxyzolamide and methazolamide, also cause potassium loss.
Diuretic-caused hypokalemia has been treated by oral ingestion of potassium, e.g. potassium chloride, but this is often not well tolerated and if not carefully controlled can produce a hyperkalemic condition with its attendant risks such as cardiac arrest.
Spironolactone [3-(3-oxo-7.alpha.-acetylthio-17.beta.-hydroxy-4-androsten-17.alpha.-yl)pr opionic acid lactone] is a diuretic acting by blocking the sodium-retaining, water-retaining and potassium excreting effect of aldosterone. Spironolactone is used in combination with hydrochlorothiazide as a diuretic which minimizes potassium loss. However, spironolactone has consistent undesirable, even unacceptable, side-effects on long-term administration.
4.alpha.,5-Epoxy-17.beta.-hydroxy-3-oxo-5.alpha.-androstane-2.alpha.carboni trile having the formula ##STR1## is disclosed in Clinton et al. U.S. Pat. No. 3,296,255, issued Jan. 3, 1967. It alters adrenal steroidogenesis and selectively blocks abnormal production of all adrenal cortical steroids, and is useful in the modulation and control of adrenocortical hyperfunction. This compound is not a diuretic per se.